Anesthesiology
-
Human umbilical cord mesenchymal stromal cells possess considerable therapeutic promise for acute respiratory distress syndrome. Umbilical cord mesenchymal stromal cells may exert therapeutic effects via extracellular vesicles, while priming umbilical cord mesenchymal stromal cells may further enhance their effect. The authors investigated whether interferon-γ-primed umbilical cord mesenchymal stromal cells would generate mesenchymal stromal cell-derived extracellular vesicles with enhanced effects in Escherichia coli (E. coli) pneumonia. ⋯ Extracellular vesicles from interferon-γ-primed human umbilical cord mesenchymal stromal cells more effectively attenuated E. coli-induced lung injury compared with extracellular vesicles from naïve mesenchymal stromal cells, potentially via enhanced macrophage phagocytosis and killing of E. coli.
-
Chronic use of μ-opioid receptor agonists paradoxically causes both hyperalgesia and the loss of analgesic efficacy. Opioid treatment increases presynaptic N-methyl-D-aspartate receptor activity to potentiate nociceptive input to spinal dorsal horn neurons. However, the mechanism responsible for this opioid-induced activation of presynaptic N-methyl-D-aspartate receptors remains unclear. α2δ-1, formerly known as a calcium channel subunit, interacts with N-methyl-D-aspartate receptors and is primarily expressed at presynaptic terminals. This study tested the hypothesis that α2δ-1-bound N-methyl-D-aspartate receptors contribute to presynaptic N-methyl-D-aspartate receptor hyperactivity associated with opioid-induced hyperalgesia and analgesic tolerance. ⋯ α2δ-1-Bound N-methyl-D-aspartate receptors contribute to opioid-induced hyperalgesia and tolerance by augmenting presynaptic N-methyl-D-aspartate receptor expression and activity at the spinal cord level.